For a number of years, attempts have been underway in various laboratories to replace Photofrin® with new porphyrin-based photosensitizers (PS). To date, most PS are amphiphilic in nature in that they contain both hydrophilic and hydrophobic substituents. Due to their π-conjugated systems, a phenomenon known as aggregation has become a concern such that it can: “decrease fluorescence quantum yields, shorten a photosensitizer's triplet excited state lifetime or reduce its photosensitizing efficiency”. Most of these compounds, therefore, are visibly aggregated in solution, so the challenge remains to be the synthesis of effective water-soluble photosensitizers that accumulate in the tumor, yet clear at a suitable time as to limit toxicity. Several researchers have either incorporated sugar residues on the periphery or ionic groups such as pyridinium, sulfonato or carboxylate groups as a means to enhance photosensitizers' aqueous solubility. The 5, 10, 15, 20-tetrakis(4-sulfonatophenyl)-porphyrin (TPPS4) is a known tetrasodium salt that although soluble in water still absorbs weakly at ˜630 nm. Core modifications have been made to TPPS4 in which chalcogen atoms such as sulfur, selenium and tellurium have aided in the water solubility of the PS, as well as, increasing the wavelength maximum to ˜695 nm. Unfortunately, these compounds were found to be toxic Therefore, the aim of the present invention was to synthesize effective and non-toxic water-soluble long wavelength absorbing photosensitizers with high singlet oxygen ability, singlet oxygen being a key cytotoxic agent for PDT.Tetrapyrollic compounds, especially porphyrin related compounds, have played a key role in developing a variety of photosensitizers. Inventors herein have recently shown that porphyrin-based compounds can also be used (i) as PET and SPECT imaging agents and (ii) as vehicles to deliver the required contrast agents (MRI, Fluorescence etc.) to image tumors. These approaches have been extremely useful in developing multimodality agents. However, one major drawback with most of these compounds is their limited solubility in water. Therefore, most of the formulations require a biocompatible surfactant, e.g. such as those commonly sold under the trademarks TWEEN-80 or CREMOPHORE. At low concentrations, such formulations are approved by FDA for clinical use, but to avoid a number of disadvantages with such formulations, it would be ‘ideal’ to design water soluble compounds for tumor imaging and therapy.
An approach for increasing the water solubility is to introduce hydrophilic substituents (e.g., —COOH, PEG, amino acids, charged species etc.) in the desired molecules. Unfortunately such incorporation can limit biological efficacy.
The following references are incorporated by reference as background art.    1. R. K. Pandey, G. Zheng The Porphyrin Handbook (Eds: Kadish, Rodgers and Smith), vol. 6, Academic Press, Boston, 2000.    2. Suresh K. Pandey, Amy L. Gryshuk, Munawwar Sajjad, Xiang Zheng, Yihui Chen, Mohei M. Abouzeid, Janet Morgan, Ivan Charamisinau, Hani A. Nabi, Allan Oseroff and Ravindra K. Pandey, Multiomodality Agents for Tumor Imaging (PET, Fluorescence) and Photodynamic Therapy: A Possible See and Treat Approach. J. Med. Chem. 2005, 48, 6286-6295.    3. Ravindra K. Pandey et al., Chlorophyll-a Analogs Conjugated with Aminophenyl-DTPA as Potential Bifunctional Agents for Magnetic Resonance Imaging and Photodynamic Therapy. Bioconjugate Chem. 2005, 16, 32-42.    4. Ravindra K. Pandey, A. B. Sumlin, W. R. Potter, D. A. Bellnier, B. W. Henderson, S. Constantine, M. Aoudia, M. R. Rodgers, K. M. Smith and T. J. Dougherty, Structure and Photodynamic Efficacy Among Alkyl Ether Analogues of Chlorophyll-a Derivatives. Photochem. Photobiol. 1996, 63, 194-205.    5. Gang Zheng, Susan Camacho, William Potter, David A. Bellnier, B. W. Henderson, Thomas J. Dougherty and Ravindra K. Pandey, Synthesis, tumor uptake and in vivo photosensitizing efficacy of a homologous series of the 3-(1′-alkoxy)ethyl-purpurin-18-N-alkylimides, J. Med. Chem., 2001, 44, 1540-1559.    6. Yihui Chen, Andrew Graham, William Potter, Janet Morgan, Lurine Vaughan, David A. Bellnier, Barbara W. Henderson, Allan Oseroff, Thomas J. Dougherty and Ravindra K. Pandey, J. Med. Chem. (Rapid Communication), 2002, 45, 255-258.